Switches.ELM

Switch #:

SWTI000678

Switch type:
Specificity

Switch subtype:
Competition

Description:
The transcriptional coactivator YAP1 and the ubiquitin ligase Itch competitively bind to the same WW-binding motif of p73. Binding of YAP1 prevents Itch-mediated ubiquitylation of p73, resulting in stabilisation, and increases trancriptional activity of p73.

Participants:
(1) Tumor protein p73 (TP73)
(2) Yorkie homolog (YAP1)
(3) E3 ubiquitin-protein ligase Itchy homolog (ITCH)

Interactions

Interaction #1 TP73 - YAP1

Is mutually exclusive with Interaction #2 TP73 - ITCH

Interfaces
(1) LIG_WW_1 motif (₄₈₄PPPY₄₈₇) in Tumor protein p73 (TP73)
(2) WW domain_(173-202) and _(232-261) in Yorkie homolog (YAP1)

Interaction Regulation
Effector binding Inhibition (E3 ubiquitin-protein ligase Itchy homolog (ITCH)) of the Tumor protein p73 (TP73) LIG_WW_1 motif - Yorkie homolog (YAP1) WW domain interaction

Interaction #2 TP73 - ITCH

Is mutually exclusive with Interaction #1 TP73 - YAP1

Interfaces
(3) LIG_WW_1 motif (₄₈₄PPPY₄₈₇) in Tumor protein p73 (TP73)
(4) WW domain_(328-357) and _(360-389) and _(440-469) and _(480-509) in E3 ubiquitin-protein ligase Itchy homolog (ITCH)

Interaction Regulation
Effector binding Inhibition (Yorkie homolog (YAP1)) of the Tumor protein p73 (TP73) LIG_WW_1 motif - E3 ubiquitin-protein ligase Itchy homolog (ITCH) WW domain interaction

Context

Switch localisation
ELM curated: cytosol, integral membrane protein, integral plasma membrane protein

Inferred: cytosol, transcription factor complex

References

(1) The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73.
Levy et al. Cell Death Differ. (2007)